Small cells, big importance

Professor Neil Watkins gave up life in the intensive care unit for the wild world of small-cell lung cancer research, fruit fly signalling pathways and controversial hypotheses

Life in the intensive care unit wasn’t exciting enough for Professor Neil Watkins.

After graduating from the University of Western Australia’s medical school in 1987 and completing his PhD in 1993, he worked as an intensive care specialist until his “light-bulb moment”.

At 31, Professor Watkins realised that his real passion lay in figuring out how things work, and he moved into the field of cancer research.

“Medicine can be a very repetitive environment”, he tells the MJA.

“I was very atypical for an intensive care specialist. I like discovering stuff and that’s the beauty of research. Essentially, I am addicted to novelty. If there’s a new idea that catches my attention, I will latch onto it.”

In 1998 Professor Watkins moved to the United States to do his postdoctoral study at the Johns Hopkins University School of Medicine, which he completed in 2003.

He stayed another six years, working on fruit fly genetics research, before returning to Australia, where he now works at the Monash Institute of Medical Research’s Centre for Cancer Research.

His focus these days is laser-like on small-cell lung cancer. He is particularly interested in pathways that regulate the formation of organs from stem cells, and how these relate to cancer.

“When tumours arise from these specialised neuroendocrine cells that make up about 1% of lung cells, they look more like brain tumours”, Professor Watkins says.

“They are very aggressive and highly lethal and make up about 15% of all lung cancers.

“Small-cell cancer tumours have a very primitive appearance on a superficial level and they have a lot of features similar to the medullablastomas that occur in children. The genetic component is different but the biology and behaviour are very similar”, he said.

“Medulloblastoma is curable, while small-cell lung cancer usually is not, but they share some common biology.

“I stumbled on this when I was working on small-cell lung cancer and my colleagues at Johns Hopkins were working on medulloblastoma.”

That conversation happened over a cup of coffee with a biochemist and a clinician in the staff lunchroom at Johns Hopkins and, since then, Professor Watkins has focused on trying to pick apart the reasons why small-cell lung cancer tumours regenerate after treatment, when medulloblastomas usually do not.

Professor Watkins says one key may be both tumour types’ relationship with the hedgehog signalling pathway — a pathway that transmits information to embryonic cells required for proper development.

“About a quarter of medulloblastomas are dependent on hedgehog signalling and they are therefore very sensitive to hedgehog inhibitors. There are Phase III clinical trials happening now on new synthetic compounds that target that pathway.

“In small-cell lung cancer, the hedgehog pathway is most important when the tumours regrow after chemotherapy.

“How do we stop them growing back? What is the difference between those cells and the rest?”

This research — the cancer stem-cell hypothesis — is controversial, Professor Watkins says.

“It is mainly the genetics establishment who object, because they think it’s all genetic, whereas the developmental biologists believe tumour growth is a function of the hierarchy of cancer cells.

“The truth, of course, is somewhere in the middle”, he says.

And that is the key to why Professor Watkins is so fascinated.

“There are so many layers of complexities to cancer. The last 10 years of research have just been the tip of the iceberg”, he says.

“The old genetic model — a cell mutates and therefore grows faster — is simple and beautiful, but it is way more complex than that.”

Professor Watkins maintains that the best research springs from basic science and, in the field of cancer, those breakthroughs have come and are coming from fields like fruit fly genetics and yeast genetics.

It’s an intense and focused life that often doesn’t leave much room for other activities.

To keep his hand in, Professor Watkins practises general medicine and teaches students for 8-week blocks through the year.

“I find it keeps me in the reality of what it’s all about — service delivery, aged care and the rest”, he says.

“I was always a nerd and a bookworm, a bit of a history buff. Sometimes I think I need to reactivate that sort of thing.